The present invention relates to mesenchymal stem cells as a vehicle for ion channel transfer in syncytial structures.
Throughout this application, various publications are referenced to by numbers. Full citations may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in the entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to those skilled therein as of the date of the invention described and claimed herein.
The pacemaker current, If, is present in both automatic (1) and non-automatic (2-6) regions of the heart. Further, the threshold voltage of activation varies widely among cardiac regions, being least negative in the sinus node (e.g. in rabbit sinus node it is −40 mV (7)) and most negative in the ventricle (−108 mV or more negative, depending on species (5,8,9)). Interestingly, the current activates at less negative voltages in the newborn ventricle (approximately −70 mV in rat (8,10)) and the diseased adult ventricle (approximately −70 mV threshold in aged hypertensive rat (11), −55 mV in failing human ventricle (12)). The molecular and cellular bases for the regional variability of activation voltages in the normal adult heart and the regulation of ventricular activation voltage by development and disease remain to be determined, but such understanding is critical to any future therapeutic application of the expressed current in myocardium.
Currently, only electronic pacemakers and cardioactive drugs are used to repair cardiac function. There is a need for a biological pacemaker in the heart that utilizes components native to the heart itself, such as alpha and beta subunits of pacemaker channel genes. (57,58,59). The present invention is directed towards perfecting a delivery system for these genes that neither requires the implantation of electronic devices, as in electronic pacemakers, nor the administration of potentially toxic chemicals, as in cardioactive drugs.